The total synthesis of maytansines (anti-tumor ansa-macrocyclic substances) is in progress. Already completed in this program is the total synthesis of (plus or minus)-N-methylmaysenine and (plus or minus)-maysine. Current and future efforts will focus on the completion of natural maytansinol, maytanacine, and maytansine. Asymmetric synthesis of maytansinol is in progress as well as resolution of racemic maytansines from the synthetic effort. A series of rational models incorporating epimeric and simplified structural features is also under synthetic study to determine the key structural parameters for anti-tumor activity. Structural modifications to eliminate clinically toxic properties of these substances is also being carried out.